Lipoprotein disorders
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Lipoprotein Disorders Microchapters |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2], Hardik Patel, M.D., Tarek Nafee, M.D. [3], Prince Tano Djan, BSc, MBChB [4], Aravind Kuchkuntla, M.B.B.S[5], Usama Talib, BSc, MD [6], Shivani Chaparala M.B.B.S [7], Vishal Devarkonda, M.B.B.S[8]
Overview
Lipoproteins are aggregates of proteins and lipids that facilitate the circulation of hydrophobic lipids in the body. Disorders of lipids and lipoproteins metabolism have important health consequences, primarily on the cardiovascular system; however, may also affect the cerebrovascular system as well as the gastrointestinal system. Lipoprotein disorders can be described as abnormalities in the level of the lipids, which include cholesterol and triglycerides, or as abnormalities in the levels of lipoproteins that include LDL, HDL, VLDL and chylomicrons.
Lipoprotein disorders (also referred to as Lipid disorders, or Dyslipidemias, or Dyslipoproteinemias) were first classified in 1967 into different phenotypes by Fredrickson according to the type of lipoproteins that are affected. This approach is considered outdated for a number of reasons. Firstly, Friedrickson's classification failed to classify disorders of low lipids. Secondly, Fredrickson's classification of hyperlipoproteinemias took into consideration the elevation in chylomicrons, LDL, VLDL but did not include abnormalities in HDL levels. Other classifications have been suggested, one of which is the National Cholesterol Education Program (NCEP) classification of lipoprotein disorders. NCEP classifies lipid disorders according to laboratory cut off points for the levels of total cholesterol, LDL-C and HDL.
Lipoprotein disorders must be initially classified broadly into hypolipidemias and hyperlipidemias corresponding to low or high lipid levels, respectively. Each of these broad categories may be further classified into primary (genetic) causes or secondary environmental causes (e.g. substance abuse, medication use, lifestyle habits, or underlying diseases etc.). Secondary causes of lipid disorders are more common and thus must be ruled out before exploring primary causes of dyslipidemia.
Classification
| Lipid disorders | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypolipoproteinemia | Hyperlipoproteinemia | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Secondary | Primary | Secondary | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Low LDL | Low HDL | Anemia, Chronic inflammation, Chronic liver disease, Hyperthyroidism, Infection, Malabsorption, Malignancy, Criticial illness, More Causes... | Alcohol, Diabetes, Drugs, Liver disease, Obesity, Renal disease, Smoking, Hypothyroidism More Causes... | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abetalipoproteinemia Hypobetalipoproteinemia PCSK9 deficiency Chylomicron retention disease Familial combined hypolipidemia | LCAT deficiency, Apolipoprotein 1 deficiency, Familial hypoalphalipoproteinemia, Tangier disease, FISH eye disease, Familial combined hypolipidemia | Type I: Familial hyperchylomicronemia | Type II | Type III: Dysbetalipoproteinemia | Type IV: Primary hypertriglyceridemia | Type V: Mixed hyperlipoproteinemia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Type A: Familial hypercholesterolemia | Type B: Familial combined hyperlipidemia | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Causes
For a complete list of causes of hyperlipoproteinemia click here.
For a complete list of causes of hypolipoproteinemia click here.
Genetics
Common Primary Lipoprotein Disorders
Shown below is a table summarizing the primary lipoprotein disorders along with the the gene and main lipoprotein involved in each disease:
| Type of lipoprotein disorder | Genetic Lipoprotein Disorder | Gene Involved | Main Lipoprotein Involved |
|---|---|---|---|
| Hyperlipoproteinemias | Familial hyperchylomicronemia Type I | ||
| Familial hypercholesterolemia Type IIA | LDL-R | LDL | |
| Familial combined hyperlipidemia Type IIB | Multiple genes | ||
| Dysbetalipoproteinemia type III | Apo E | ||
| Familial hypertriglyceridemia Type IV | Multiple genes | ||
| Mixed hyperlipoproteinemia Type V | APOA5 | VLDL, CHYLOMICRONS | |
| Hypolipoproteinemias | Abetalipoproteinemia | MTP | LDL |
| Hypobetalipoproteinemia | Apo B | LDL | |
| Familial hypoalphalipoproteinemia | |||
| Tangier disease | ABCA1 | HDL | |
| Familial LCAT deficiency | LCAT | HDL | |
| PCSK9 deficiency | PCSK9 | HDL | |
| Chylomicron retention disease | SAR1B | Multiple |
Rare Primary Lipoprotein Disorders
| Type of lipoprotein disorder | Genetic Lipoprotein Disorder | Gene Involved | Main Lipoprotein Involved |
|---|---|---|---|
| Hyperlipoproteinemias | Autosomal dominant hypercholesterolemia | PCSK9 | LDL |
| Autosomal recessive hypercholesterolemia | ARH | LDL | |
| Familial sitosterolemia | ABCG5 - ABCG8 | LDL | |
| Familial lipoprotein(a) hyperlipoproteinemia | Apo(a) | LDL | |
| Familial defective apo B100 | Apo B | LDL | |
| Hepatic lipase deficiency | HL | ||
| Lipoprotein lipase deficiency | LPL | Chylomicron | |
| Apo C-II deficiency | Apo C-II | Chylomicron | |
| Apo A-V deficiency | Apo A-V deficiency | Chylomicron | |
| Hypolipoproteinemias | Familial hypoalphalipoproteinemia | ||
| GPIHBP1 deficiency | GPIHBP1 | Chylomicron | |
| Apo A-I deficiency | Apo A-I | HDL | |
| CETP deficiency | CETP | HDL | |
| Niemann-Pick disease | SMPD1, NPC1 | HDL |